Pub Date : 2025-12-01DOI: 10.1016/S2451-9022(25)00343-X
{"title":"Guide for Authors","authors":"","doi":"10.1016/S2451-9022(25)00343-X","DOIUrl":"10.1016/S2451-9022(25)00343-X","url":null,"abstract":"","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 12","pages":"Pages A5-A10"},"PeriodicalIF":4.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145665609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.bpsc.2024.08.002
Dore Loef , Philip F.P. van Eijndhoven , Sigfried N.T.M. Schouws , Arjen J.C. Slooter , Nikki Janssen , Rob M. Kok , Bart P.F. Rutten , Eric van Exel , Didi Rhebergen , Mardien L. Oudega , Roel J.T. Mocking , Indira Tendolkar , Annemiek Dols , Esmée Verwijk
Background
Monitoring cognitive side effects following electroconvulsive therapy (ECT) is crucial for balancing side effects and clinical effectiveness. Yet, evidence-based guidelines on cognitive testing following ECT are lacking. A frequently used test in global ECT practice is the Mini-Mental State Examination (MMSE). We examined the change of the MMSE score and its performance in identifying a decline in predefined neuropsychological measures sensitive to ECT-induced cognitive changes: verbal recall and verbal fluency.
Methods
Mean MMSE scores before and 1 week after ECT were compared using a Wilcoxon signed rank test. The Reliable Change Index was calculated for all cognitive measures to indicate whether a participant’s change in score from pre- to post-ECT was considered statistically significant. The sensitivity and specificity of the MMSE were calculated.
Results
A total of 426 patients with depression from 5 sites were included from the Dutch ECT Consortium. Mean (SD) MMSE score increased significantly from 26.2 (3.9) before ECT to 26.8 (3.8) after ECT (p = .002). After ECT, 36 patients (8.5%) showed a significant decline in MMSE score. The sensitivity of the MMSE in identifying patients who experienced a significant decline in verbal recall or verbal fluency ranged from 3.6% to 11.1%. The specificity of the MMSE in identifying patients who did not experience a significant decline in verbal recall or verbal fluency ranged from 95.6% to 96.6%.
Conclusions
Given the very low sensitivity of the MMSE, we propose reconsidering the prominence of the MMSE in ECT practice and cognitive monitoring guidelines, advocating for a more comprehensive approach to assess ECT-induced cognitive changes.
{"title":"The Sensitivity of the Mini-Mental State Examination to Detect Objective Cognitive Side Effects Induced by Electroconvulsive Therapy: Results From the Dutch ECT Consortium","authors":"Dore Loef , Philip F.P. van Eijndhoven , Sigfried N.T.M. Schouws , Arjen J.C. Slooter , Nikki Janssen , Rob M. Kok , Bart P.F. Rutten , Eric van Exel , Didi Rhebergen , Mardien L. Oudega , Roel J.T. Mocking , Indira Tendolkar , Annemiek Dols , Esmée Verwijk","doi":"10.1016/j.bpsc.2024.08.002","DOIUrl":"10.1016/j.bpsc.2024.08.002","url":null,"abstract":"<div><h3>Background</h3><div>Monitoring cognitive side effects following electroconvulsive therapy (ECT) is crucial for balancing side effects and clinical effectiveness. Yet, evidence-based guidelines on cognitive testing following ECT are lacking. A frequently used test in global ECT practice is the Mini-Mental State Examination (MMSE). We examined the change of the MMSE score and its performance in identifying a decline in predefined neuropsychological measures sensitive to ECT-induced cognitive changes: verbal recall and verbal fluency.</div></div><div><h3>Methods</h3><div>Mean MMSE scores before and 1 week after ECT were compared using a Wilcoxon signed rank test. The Reliable Change Index was calculated for all cognitive measures to indicate whether a participant’s change in score from pre- to post-ECT was considered statistically significant. The sensitivity and specificity of the MMSE were calculated.</div></div><div><h3>Results</h3><div>A total of 426 patients with depression from 5 sites were included from the Dutch ECT Consortium. Mean (SD) MMSE score increased significantly from 26.2 (3.9) before ECT to 26.8 (3.8) after ECT (<em>p</em> = .002). After ECT, 36 patients (8.5%) showed a significant decline in MMSE score. The sensitivity of the MMSE in identifying patients who experienced a significant decline in verbal recall or verbal fluency ranged from 3.6% to 11.1%. The specificity of the MMSE in identifying patients who did not experience a significant decline in verbal recall or verbal fluency ranged from 95.6% to 96.6%.</div></div><div><h3>Conclusions</h3><div>Given the very low sensitivity of the MMSE, we propose reconsidering the prominence of the MMSE in ECT practice and cognitive monitoring guidelines, advocating for a more comprehensive approach to assess ECT-induced cognitive changes.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 12","pages":"Pages 1268-1275"},"PeriodicalIF":4.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.bpsc.2024.09.010
Chen Zhang , Zongfeng Zhang , Rui Gao , Yongjun Chen , Xuan Cao , Xianghan Yi , Qing Fan
Background
Obsessive-compulsive disorder (OCD) is often comorbid with obsessive-compulsive personality disorder (OCPD). The relationship between OCD and OCPD is complex, and the impact of comorbid OCPD on OCD remains underexplored, necessitating further research. In this study, we aimed to investigate the clinical correlates and brain morphometries associated with comorbid OCPD in a large sample of unmedicated patients with OCD.
Methods
A total of 248 unmedicated patients diagnosed with OCD (45 comorbid with OCPD) were included in this study. All participants were assessed for OCD symptoms, OCPD traits, obsessive beliefs, depression, and anxiety. Among them, 145 patients (23 comorbid with OCPD) volunteered to receive magnetic resonance imaging brain scans.
Results
Approximately 18% (45/248) of patients with OCD were comorbid for OCPD (OCD+OCPD). Patients with OCD+OCPD exhibited more severe OCD symptoms, obsessive beliefs, depression, and anxiety than OCD patients without OCPD. Additionally, the severity of OCPD was positively correlated with OCD symptoms and obsessive beliefs. Furthermore, patients with OCD+OCPD exhibited increased cortical complexity in the left superior parietal lobule and left precuneus, which mediated the relationship between OCPD and OCD symptoms only in OCD patients without OCPD.
Conclusions
The co-occurrence of OCPD may contribute to the heightened severity of psychopathological symptoms and associated brain morphological alterations in patients with OCD, indicating distinct but interrelated constructs between these 2 disorders.
{"title":"Obsessive-Compulsive Disorder Comorbid With or Without Obsessive-Compulsive Personality Disorder: Conceptual Implications, Clinical Correlates, and Brain Morphometries","authors":"Chen Zhang , Zongfeng Zhang , Rui Gao , Yongjun Chen , Xuan Cao , Xianghan Yi , Qing Fan","doi":"10.1016/j.bpsc.2024.09.010","DOIUrl":"10.1016/j.bpsc.2024.09.010","url":null,"abstract":"<div><h3>Background</h3><div>Obsessive-compulsive disorder (OCD) is often comorbid with obsessive-compulsive personality disorder (OCPD). The relationship between OCD and OCPD is complex, and the impact of comorbid OCPD on OCD remains underexplored, necessitating further research. In this study, we aimed to investigate the clinical correlates and brain morphometries associated with comorbid OCPD in a large sample of unmedicated patients with OCD.</div></div><div><h3>Methods</h3><div><span>A total of 248 unmedicated patients diagnosed with OCD (45 comorbid with OCPD) were included in this study. All participants were assessed for OCD symptoms, OCPD traits, obsessive beliefs, depression, and anxiety. Among them, 145 patients (23 comorbid with OCPD) volunteered to receive magnetic resonance imaging </span>brain scans.</div></div><div><h3>Results</h3><div><span>Approximately 18% (45/248) of patients with OCD were comorbid for OCPD (OCD+OCPD). Patients with OCD+OCPD exhibited more severe OCD symptoms, obsessive beliefs, depression, and anxiety than OCD patients without OCPD. Additionally, the severity of OCPD was positively correlated with OCD symptoms and obsessive beliefs. Furthermore, patients with OCD+OCPD exhibited increased cortical complexity in the left </span>superior parietal lobule<span> and left precuneus, which mediated the relationship between OCPD and OCD symptoms only in OCD patients without OCPD.</span></div></div><div><h3>Conclusions</h3><div>The co-occurrence of OCPD may contribute to the heightened severity of psychopathological symptoms and associated brain morphological alterations in patients with OCD, indicating distinct but interrelated constructs between these 2 disorders.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 12","pages":"Pages 1276-1283"},"PeriodicalIF":4.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.bpsc.2025.10.003
Camilo de la Fuente-Sandoval
{"title":"Neuroimaging and Glutamatergic Trials in Psychosis: Where Are We Standing, and Where Do We Go Now?","authors":"Camilo de la Fuente-Sandoval","doi":"10.1016/j.bpsc.2025.10.003","DOIUrl":"10.1016/j.bpsc.2025.10.003","url":null,"abstract":"","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 12","pages":"Pages 1213-1214"},"PeriodicalIF":4.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145665611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.bpsc.2025.03.013
Akihiro Takamiya , Thomas Vande Casteele , Filip Bouckaert , Margot G.A. Van Cauwenberge , Maarten Laroy , François-Laurent De Winter , Patrick Dupont , Jan Van den Stock , Michel Koole , Koen Van Laere , Louise Emsell , Mathieu Vandenbulcke
Background
Late-life depression (LLD) is associated with white matter (WM) alterations. Current evidence indicates that amyloid positron emission tomography (PET) tracers are sensitive and reliable markers for evaluating normal-appearing WM (NAWM) on magnetic resonance imaging (MRI), showing an association between lower uptake and Alzheimer’s disease pathology and higher uptake with age-related changes. Utilizing this novel and reliable technique, we aimed to distinguish between 2 hypothetical models for neurobiology of LLD, the pathological neurodegenerative model and the accelerated aging model.
Methods
In this monocentric cross-sectional study, a total of 103 participants, including 61 patients with LLD (age 73.8 ± 7.0 years; 41 female) and 42 healthy control (HC) participants (age 72.5 ± 7.6 years; 28 female), underwent PET imaging with 18F-flutemetamol, MRI, and clinical assessment. T2-weighted fluid-attenuated inversion recovery images were segmented into WM hyperintensities (WMHs) and NAWM.
Results
The 18F-flutemetamol standardized uptake value ratio (SUVR) in WMHs was significantly lower than that in NAWM (t102 = 7.8, p < .001). Compared with HC participants, patients with LLD exhibited higher 18F-flutemetamol SUVR in both NAWM (p < .001, Cohen’s d = 0.91) and WMHs (p = .005, d = 0.56), even after controlling for age and 18F-flutemetamol SUVR in cortical gray matter.
Conclusions
Our result of elevated 18F-flutemetamol uptake in NAWM is not consistent with the pathological neurodegenerative aging pattern observed in Alzheimer’s disease but is consistent with patterns of age-related changes. This distinction is crucial for the development of future targeted treatments.
{"title":"Accelerated Aging of White Matter in Late-Life Depression: Evidence From 18F-Flutemetamol Positron Emission Tomography Imaging","authors":"Akihiro Takamiya , Thomas Vande Casteele , Filip Bouckaert , Margot G.A. Van Cauwenberge , Maarten Laroy , François-Laurent De Winter , Patrick Dupont , Jan Van den Stock , Michel Koole , Koen Van Laere , Louise Emsell , Mathieu Vandenbulcke","doi":"10.1016/j.bpsc.2025.03.013","DOIUrl":"10.1016/j.bpsc.2025.03.013","url":null,"abstract":"<div><h3>Background</h3><div><span>Late-life depression (LLD) is associated with white matter (WM) alterations. Current evidence indicates that amyloid positron emission tomography (PET) </span>tracers are sensitive and reliable markers for evaluating normal-appearing WM (NAWM) on magnetic resonance imaging (MRI), showing an association between lower uptake and Alzheimer’s disease pathology and higher uptake with age-related changes. Utilizing this novel and reliable technique, we aimed to distinguish between 2 hypothetical models for neurobiology of LLD, the pathological neurodegenerative model and the accelerated aging model.</div></div><div><h3>Methods</h3><div>In this monocentric cross-sectional study, a total of 103 participants, including 61 patients with LLD (age 73.8 ± 7.0 years; 41 female) and 42 healthy control (HC) participants (age 72.5 ± 7.6 years; 28 female), underwent PET imaging with <sup>18</sup>F-flutemetamol, MRI, and clinical assessment. T2-weighted fluid-attenuated inversion recovery images were segmented into WM hyperintensities (WMHs) and NAWM.</div></div><div><h3>Results</h3><div>The <sup>18</sup><span>F-flutemetamol standardized uptake value ratio (SUVR) in WMHs was significantly lower than that in NAWM (</span><em>t</em><sub>102</sub> = 7.8, <em>p</em> < .001). Compared with HC participants, patients with LLD exhibited higher <sup>18</sup>F-flutemetamol SUVR in both NAWM (<em>p</em> < .001, Cohen’s <em>d</em> = 0.91) and WMHs (<em>p</em> = .005, <em>d</em> = 0.56), even after controlling for age and <sup>18</sup>F-flutemetamol SUVR in cortical gray matter.</div></div><div><h3>Conclusions</h3><div>Our result of elevated <sup>18</sup><span>F-flutemetamol uptake in NAWM is not consistent with the pathological neurodegenerative aging pattern observed in Alzheimer’s disease but is consistent with patterns of age-related changes. This distinction is crucial for the development of future targeted treatments.</span></div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 12","pages":"Pages 1294-1301"},"PeriodicalIF":4.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.bpsc.2024.06.013
Qingwen Ding , Xinying Li , Divyangana Rakesh , Siya Peng , Jiahua Xu , Jie Chen , Nengzhi Jiang , Yu Luo , Xuebing Li , Shaozheng Qin , Sarah Whittle
Background
Adolescents raised in families with different maternal and paternal parenting combinations exhibit variations in neurocognition and psychopathology; however, whether neural differences exist remains unexplored. This study used a longitudinal twin sample to delineate how different parenting combinations influence adolescent brain structure and to elucidate the genetic contribution.
Methods
A cohort of 216 twins participated in parenting assessments during early adolescence and underwent magnetic resonance imaging scanning during middle adolescence. We utilized latent profile analysis to distinguish between various maternal and paternal parenting profiles and subsequently investigated their influences on brain anatomy. Biometric analysis was applied to assess genetic influences on brain structure, and associations with internalizing symptoms were explored.
Results
In early adolescence, 4 parenting profiles emerged, which were characterized by levels of harshness and hostility in one or both parents. Compared with adolescents in “catparent” families (low harshness/hostility in both parents), those raised in “tigermom” families (harsh/hostile mother only) exhibited a smaller nucleus accumbens volume and larger temporal cortex surface area; those in “tigerdad” families demonstrated larger thalamus volumes; and those in “tigerparent” families displayed smaller volumes in the midanterior corpus callosum. Genetic risk factors contributed significantly to the observed brain structural heterogeneity and internalizing symptoms. However, the influences of parenting profiles and brain structure on internalizing symptoms were not significant.
Conclusions
The findings underscore distinct brain structural features linked to maternal and paternal parenting combinations, particularly in terms of subcortical volume and cortical surface area. This study suggests an interdependent role of maternal and paternal parenting in shaping adolescent neurodevelopment.
{"title":"The Influence of Maternal and Paternal Parenting on Adolescent Brain Structure","authors":"Qingwen Ding , Xinying Li , Divyangana Rakesh , Siya Peng , Jiahua Xu , Jie Chen , Nengzhi Jiang , Yu Luo , Xuebing Li , Shaozheng Qin , Sarah Whittle","doi":"10.1016/j.bpsc.2024.06.013","DOIUrl":"10.1016/j.bpsc.2024.06.013","url":null,"abstract":"<div><h3>Background</h3><div><span>Adolescents raised in families with different maternal and paternal parenting combinations exhibit variations in neurocognition and psychopathology; however, whether neural differences exist remains unexplored. This study used a longitudinal twin sample to delineate how different parenting combinations influence adolescent brain structure and to elucidate the </span>genetic contribution.</div></div><div><h3>Methods</h3><div>A cohort of 216 twins participated in parenting assessments during early adolescence and underwent magnetic resonance imaging scanning during middle adolescence. We utilized latent profile analysis<span><span> to distinguish between various maternal and paternal parenting profiles and subsequently investigated their influences on brain anatomy. </span>Biometric analysis was applied to assess genetic influences on brain structure, and associations with internalizing symptoms were explored.</span></div></div><div><h3>Results</h3><div><span>In early adolescence, 4 parenting profiles emerged, which were characterized by levels of harshness and hostility in one or both parents. Compared with adolescents in “catparent” families (low harshness/hostility in both parents), those raised in “tigermom” families (harsh/hostile mother only) exhibited a smaller nucleus accumbens<span> volume and larger temporal cortex<span> surface area; those in “tigerdad” families demonstrated larger </span></span></span>thalamus<span> volumes; and those in “tigerparent” families displayed smaller volumes in the midanterior corpus callosum<span>. Genetic risk factors contributed significantly to the observed brain structural heterogeneity and internalizing symptoms. However, the influences of parenting profiles and brain structure on internalizing symptoms were not significant.</span></span></div></div><div><h3>Conclusions</h3><div>The findings underscore distinct brain structural features linked to maternal and paternal parenting combinations, particularly in terms of subcortical volume and cortical surface area. This study suggests an interdependent role of maternal and paternal parenting in shaping adolescent neurodevelopment.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 12","pages":"Pages 1249-1257"},"PeriodicalIF":4.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.bpsc.2025.07.004
Ioana Varvari , Lara Bolte , Chiara Colli , Valentina Mancini , Matthew M. Nour , Philip McGuire , Robert A. McCutcheon
Aberrant dopamine and glutamate signaling are implicated in the pathophysiology of schizophrenia. Existing treatments primarily target dopamine pathways underlying positive symptoms but have relatively little effect on cognitive and negative symptoms. Glutamatergic modulators may treat the latter symptom domains, and neuroimaging studies have the potential to identify therapeutic mechanisms. We conducted a systematic review to examine functional neuroimaging studies of glutamatergic modulators in psychosis and determine whether these agents alter brain activity, chemistry, or functional connectivity and whether such changes map onto clinical outcomes. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO: CRD42024549120), MEDLINE, Embase, and PsycInfo were searched from inception to June 2024 for studies administering pharmacologic glutamate modulators to individuals with psychosis, using functional neuroimaging (proton magnetic resonance spectroscopy [1H-MRS], functional magnetic resonance imaging [fMRI], arterial spin labeling, positron emission tomography, electroencephalography [EEG], or magnetoencephalography). Twenty-seven articles met inclusion criteria, encompassing 841 participants. Evidence from 1H-MRS suggests that sarcosine, N-acetylcysteine, and riluzole reduce glutamate concentrations in frontal and hippocampal regions, but clinical outcomes have not been investigated. Resting-state and task-based fMRI studies suggest that NMDA receptor modulators may normalize measures of functional dysconnectivity, although effects were often short-lived and did not always correspond to sustained symptom improvements. Similarly, EEG studies consistently identified normalization of mismatch negativity and gamma oscillations, but correlations with symptom or cognitive outcomes were inconsistent. While glutamatergic modulators show measurable effects on brain chemistry and electrophysiology, the relationship to robust, durable clinical benefits remains elusive. Future work should use larger, longer-duration, and multimodal imaging studies to clarify the precise mechanisms, optimal dosing, and the patient subgroups most likely to benefit from glutamatergic interventions in psychosis.
{"title":"Glutamatergic Modulation of Brain Function in Psychosis: A Systematic Review of Neuroimaging Studies","authors":"Ioana Varvari , Lara Bolte , Chiara Colli , Valentina Mancini , Matthew M. Nour , Philip McGuire , Robert A. McCutcheon","doi":"10.1016/j.bpsc.2025.07.004","DOIUrl":"10.1016/j.bpsc.2025.07.004","url":null,"abstract":"<div><div>Aberrant dopamine and glutamate signaling are implicated in the pathophysiology of schizophrenia. Existing treatments primarily target dopamine pathways underlying positive symptoms but have relatively little effect on cognitive and negative symptoms. Glutamatergic modulators may treat the latter symptom domains, and neuroimaging studies have the potential to identify therapeutic mechanisms. We conducted a systematic review to examine functional neuroimaging studies of glutamatergic modulators in psychosis and determine whether these agents alter brain activity, chemistry, or functional connectivity and whether such changes map onto clinical outcomes. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO: <span><span>CRD42024549120</span><svg><path></path></svg></span>), MEDLINE, Embase, and PsycInfo were searched from inception to June 2024 for studies administering pharmacologic glutamate modulators to individuals with psychosis, using functional neuroimaging (proton magnetic resonance spectroscopy [<sup>1</sup>H-MRS], functional magnetic resonance imaging [fMRI], arterial spin labeling, positron emission tomography, electroencephalography [EEG], or magnetoencephalography). Twenty-seven articles met inclusion criteria, encompassing 841 participants. Evidence from <sup>1</sup>H-MRS suggests that sarcosine, <em>N</em>-acetylcysteine, and riluzole reduce glutamate concentrations in frontal and hippocampal regions, but clinical outcomes have not been investigated. Resting-state and task-based fMRI studies suggest that NMDA receptor modulators may normalize measures of functional dysconnectivity, although effects were often short-lived and did not always correspond to sustained symptom improvements. Similarly, EEG studies consistently identified normalization of mismatch negativity and gamma oscillations, but correlations with symptom or cognitive outcomes were inconsistent. While glutamatergic modulators show measurable effects on brain chemistry and electrophysiology, the relationship to robust, durable clinical benefits remains elusive. Future work should use larger, longer-duration, and multimodal imaging studies to clarify the precise mechanisms, optimal dosing, and the patient subgroups most likely to benefit from glutamatergic interventions in psychosis.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 12","pages":"Pages 1221-1238"},"PeriodicalIF":4.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.bpsc.2025.02.013
Joseph Aloi , Tahlia E. Korin , Olivia K. Murray , Kathleen I. Crum , Katherine LeFevre , Mario Dzemidzic , Leslie A. Hulvershorn
Background
Children with externalizing disorders often have difficulties with impulsivity (IMP) and emotion regulation (ER). These constructs have been associated with dysfunction in the recruitment of reward-processing circuits and striatal connectivity with cortical networks. However, it is unclear to what extent co-presentations of IMP and ER are associated with differences in striatocortical connectivity.
Methods
In study 1, a latent profile analysis (LPA) was conducted in a sample of 198 youths with externalizing disorders (oppositional defiant disorder and/or conduct disorder) to investigate co-presentation of IMP and ER symptoms. Participants completed the UPPS Impulsivity Scale (UPPS) and the Emotion Regulation Checklist (ERC). LPA was applied to the subscales of the UPPS and ERC. In study 2, we examined 169 participants who completed a resting-state functional magnetic resonance imaging scan to examine differences in striatocortical connectivity between profiles.
Results
The LPA identified 3 profiles: moderate IMP/moderate ER, high IMP/low ER, and high IMP/moderate ER. The 2 high IMP profiles were associated with greater connectivity between the posterior caudate nucleus and parietal cortex. The high IMP/low ER profile was associated with increased connectivity between the anterior caudate and anterior insula.
Conclusions
The current data indicate that the profiles associated with high IMP are associated with greater caudate–parietal cortex connectivity, while the profile associated with high IMP and impaired ER showed increased anterior caudate–anterior insular cortex connectivity. The current work contributes to the literature by examining the relationship between heterogeneity of externalizing symptoms and functional connectivity.
{"title":"Latent Profiles of Impulsivity and Emotion Regulation in Children With Externalizing Disorders Are Associated With Alterations in Striatocortical Connectivity","authors":"Joseph Aloi , Tahlia E. Korin , Olivia K. Murray , Kathleen I. Crum , Katherine LeFevre , Mario Dzemidzic , Leslie A. Hulvershorn","doi":"10.1016/j.bpsc.2025.02.013","DOIUrl":"10.1016/j.bpsc.2025.02.013","url":null,"abstract":"<div><h3>Background</h3><div>Children with externalizing disorders often have difficulties with impulsivity (IMP) and emotion regulation (ER). These constructs have been associated with dysfunction in the recruitment of reward-processing circuits and striatal connectivity with cortical networks. However, it is unclear to what extent co-presentations of IMP and ER are associated with differences in striatocortical connectivity.</div></div><div><h3>Methods</h3><div>In study 1, a latent profile analysis (LPA) was conducted in a sample of 198 youths with externalizing disorders (oppositional defiant disorder and/or conduct disorder) to investigate co-presentation of IMP and ER symptoms. Participants completed the UPPS Impulsivity Scale (UPPS) and the Emotion Regulation Checklist (ERC). LPA was applied to the subscales of the UPPS and ERC. In study 2, we examined 169 participants who completed a resting-state functional magnetic resonance imaging scan to examine differences in striatocortical connectivity between profiles.</div></div><div><h3>Results</h3><div><span><span>The LPA identified 3 profiles: moderate IMP/moderate ER, high IMP/low ER, and high IMP/moderate ER. The 2 high IMP profiles were associated with greater connectivity between the posterior caudate nucleus and </span>parietal cortex. The high IMP/low ER profile was associated with increased connectivity between the anterior caudate and anterior </span>insula.</div></div><div><h3>Conclusions</h3><div><span>The current data indicate that the profiles associated with high IMP are associated with greater caudate–parietal cortex connectivity, while the profile associated with high IMP and impaired ER showed increased anterior caudate–anterior insular cortex connectivity. The current work contributes to the literature by examining the relationship between heterogeneity of externalizing symptoms and </span>functional connectivity.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 12","pages":"Pages 1258-1267"},"PeriodicalIF":4.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.bpsc.2025.06.003
Drew E. Winters, Joseph P. Schacht
Background
Dysregulation of inhibitory control is a core feature of alcohol use disorder (AUD) and is mediated, in part, by catechol-O-methyltransferase (COMT) regulation of cortical dopaminergic neurotransmission. Tolcapone, a brain-penetrant COMT inhibitor, potentiates evoked dopamine release and may improve inhibitory control in AUD.
Methods
Non–treatment-seeking participants with AUD (N = 64) were randomized to tolcapone (titrated to 200 mg three times a day) or placebo for 8 days and completed a functional magnetic resonance imaging stop signal task on study days 1 (prior to medication ingestion) and 7. Brain areas in which activation for the contrast of successful versus unsuccessful stop trials (stop success [SS]>stop error [SE]) differed between medication groups on day 7 relative to day 1 were identified. Activation of these areas and their functional connectivity with other areas were tested for association with changes in drinking during the medication period and with changes in stop signal reaction time, a behavioral index of inhibitory control.
Results
The tolcapone group demonstrated greater SS>SE activation in the right dorsolateral prefrontal cortex and inferior frontal gyrus (iFG). In the tolcapone group, greater activation of both areas was associated with improved inhibitory control, and greater iFG activation was associated with reduced drinking. Increased connectivity between the iFG and right anterior insula was associated with reduced drinking, and increased connectivity between the iFG and anterior cingulate cortex was associated with improved inhibitory control.
Conclusions
Tolcapone increased activation of cortical areas implicated in inhibitory control. The associations between increased iFG activation and connectivity, improved inhibitory control, and reduced drinking suggest that pharmacological interventions that increase cortical dopamine may rescue dysregulated inhibitory control among people with AUD.
背景:抑制控制失调是酒精使用障碍(AUD)的核心特征,部分是由儿茶酚- o -甲基转移酶(COMT)调节皮质多巴胺能神经传递介导的。Tolcapone是一种脑渗透性COMT抑制剂,可增强诱发多巴胺释放,并可能改善AUD的抑制控制。方法:未寻求治疗的AUD患者(n=64)被随机分配到托尔卡彭组(每日滴药200 mg)或安慰剂组8天,并在研究第1天(服药前)和第7天完成fMRI停止信号任务。确定了第7天与第1天相比,药物组之间成功与不成功停止试验对比(SS>SE)的激活不同的脑区域。研究人员测试了这些区域的激活以及它们与其他区域的功能连接与服药期间饮酒变化和停止信号反应时间(抑制控制的一种行为指标)之间的关系。结果:托尔卡酮组右背外侧前额叶皮层和额下回(iFG)的SS>SE激活明显增加。在托尔卡彭组中,这两个区域的更大激活与抑制控制的改善有关,iFG的更大激活与饮酒的减少有关。iFG和右前叶岛之间的连接增加与饮酒减少有关,iFG和前扣带皮层之间的连接增加与抑制控制改善有关。结论:托尔卡彭增加了与抑制控制有关的皮质区域的激活。iFG激活增加与连通性、抑制控制改善和饮酒减少之间的关联表明,增加皮质多巴胺的药物干预可能挽救AUD患者抑制控制失调。
{"title":"Effects of COMT Suppression in a Randomized Trial on the Neural Correlates of Inhibitory Processing Among People With Alcohol Use Disorder","authors":"Drew E. Winters, Joseph P. Schacht","doi":"10.1016/j.bpsc.2025.06.003","DOIUrl":"10.1016/j.bpsc.2025.06.003","url":null,"abstract":"<div><h3>Background</h3><div>Dysregulation of inhibitory control is a core feature of alcohol use disorder (AUD) and is mediated, in part, by catechol-<em>O</em>-methyltransferase (COMT) regulation of cortical dopaminergic neurotransmission. Tolcapone, a brain-penetrant COMT inhibitor, potentiates evoked dopamine release and may improve inhibitory control in AUD.</div></div><div><h3>Methods</h3><div>Non–treatment-seeking participants with AUD (<em>N</em> = 64) were randomized to tolcapone (titrated to 200 mg three times a day) or placebo for 8 days and completed a functional magnetic resonance imaging stop signal task on study days 1 (prior to medication ingestion) and 7. Brain areas in which activation for the contrast of successful versus unsuccessful stop trials (stop success [SS]>stop error [SE]) differed between medication groups on day 7 relative to day 1 were identified. Activation of these areas and their functional connectivity with other areas were tested for association with changes in drinking during the medication period and with changes in stop signal reaction time, a behavioral index of inhibitory control.</div></div><div><h3>Results</h3><div>The tolcapone group demonstrated greater SS>SE activation in the right dorsolateral prefrontal cortex and inferior frontal gyrus (iFG). In the tolcapone group, greater activation of both areas was associated with improved inhibitory control, and greater iFG activation was associated with reduced drinking. Increased connectivity between the iFG and right anterior insula was associated with reduced drinking, and increased connectivity between the iFG and anterior cingulate cortex was associated with improved inhibitory control.</div></div><div><h3>Conclusions</h3><div>Tolcapone increased activation of cortical areas implicated in inhibitory control. The associations between increased iFG activation and connectivity, improved inhibitory control, and reduced drinking suggest that pharmacological interventions that increase cortical dopamine may rescue dysregulated inhibitory control among people with AUD.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 12","pages":"Pages 1302-1312"},"PeriodicalIF":4.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}